New Risk Assessment Tool for White Women Includes Common Genetic Variants, but May Be More Useful for Understanding Population Trends

Doctors use risk assessment tools to calculate breast cancer risk. Two of the most well-known are the Gail model and the Breast Cancer Surveillance Consortium (BCSC) Risk Calculator.

The Gail model assesses breast cancer risk based on a series of personal health questions that women and their doctors answer together. The questions ask about risk factors such as age, child-bearing history, family history of breast cancer, and breast biopsy results. Some more recent versions of the Gail model ask about alcohol use, menopausal status, and body mass index. The result is a Gail score, which estimates the risk of developing invasive breast cancer in the next 5 years.

The BCSC Risk Calculator is designed to be used by doctors to assess the risk of breast cancer in women:

who have never been diagnosed with breast cancer or DCIS

between the ages of 35 and 74

who have never had breast augmentation

who have never had a mastectomy

The BCSC Risk Calculator is the only risk assessment tool that includes breast density information when calculating risk.

Researchers know that certain genetic variants, called single nucleotide polymorphisms (SNPs), are linked to a higher risk of breast cancer. Still, each SNP contributes only a tiny amount to a person’s overall risk of developing breast cancer.

SNPs are the most common type of genetic variant. Each SNP is a difference in a single building block of DNA (called a nucleotide). SNPs happen normally in our DNA -- scientists estimate that a SNP happens once in every 300 nucleotides, which means there are about 10 million SNPs in the human genome. Most SNPs have no effect on health or development, but some, like the ones associated with breast cancer, may have health implications.

Researchers have created a new risk assessment tool for white women in the United States that includes 92 breast cancer susceptibility SNPs.

To create the risk assessment tool, the researchers used data from large, prospective studies on breast cancer with well-documented outcomes, including information from 17,171 women diagnosed with breast cancer and 19,862 controls from the Breast and Prostate Cancer Cohort Consortium study and 5,879 women participating in the 2010 National Health Interview Survey.

Information on both modifiable and nonmodifiable risk factors was included in the risk assessment tool. Nonmodifiable risk factors included:

92 SNPs

family history

height

age at first period

age at menopause

age at first live birth

Modifiable risk factors included:

body mass index

alcohol use

smoking

taking hormone replacement therapy during menopause

Using their model, the researchers estimated that 27% of all breast cancers in white women in the United States could be prevented if women maintained a lean to average body mass index and didn’t drink, smoke, or use hormone replacement therapy.

Women who had the highest risk based on nonmodifiable risk factors got the biggest reduction in risk from modifying the risk factors that could be changed.

While including information on the 92 SNPs adds more information to the risk assessment tool and would seem to make it more robust, there have been some questions about how the researchers added this information to the tool.

Information on 68 of the 92 SNPs wasn’t collected. Instead, the researchers “simulated a risk score for the missing 68 SNPs using estimates of associations between these SNPs and case-control status and family history.”

In an accompanying editorial, Drs. William Dupont, Jeffrey Blume, and Jeffrey Smith, of Vanderbilt University, write about the missing information: “This suggests that the model may best be used to predict and to understand population trends that could be the subject of large publish health interventions, as opposed to using it as a risk score calculator to inform a clinical decision for a specific patient.”

If you have a higher-than-average risk of breast cancer, you and your doctor will develop a screening plan tailored to your unique situation. General recommended screening guidelines include:

a monthly breast self-exam

a yearly breast exam by your doctor

a digital mammogram every year starting at age 40

Your personal screening plan also may include:

MRI

ultrasound

Talk to your doctor about developing a specialized program for early detection that meets your individual needs and gives you peace of mind.

It also makes good sense to do all that you can to keep your risk of breast cancer as low as it can be. Some lifestyle choices you may want to consider are: